740
healthy and heterozygous for CF. The finding that unaffected heterozygous children of women with CF are mainly male was unexpected. The mechanism for this male dominance remains were
obscure. The two North American studies did not state the sex of the infants,2,3 and other reports provide such data only for families of children with CF, and not for children of CF mothers. Tests on healthy siblings of CF patients showed an unexpected sex ratio, with an excess of heterozygous boys inheriting the CF gene either from their father or their mother.4,5 Investigations of siblings with partners heterozygous for CF make a sex-related selection after fertilisation probable.6 However, a sex-related selective influence before fertilisation may occur as a result of the highly viscous, low-water-content cervical mucus of women with CF, which may form a barrier to sperm. A hitherto unknown heterozygous advantage might be present in Y chromosome carriers. Clinic for Child and Youth Medicine, Im Borntal 1-7, W-3423 Bad Sachsa, Germany
O. METZ
1. Metz OW, Metz S. Schwangerschaft und Geburt bei Mukoviszidose: Resultate der Deutschland-Studie. Klin Paed (in press). 2. Cohen LF, DiSant’Agnese PA, Friedlander J. Cystic fibrosis and pregnancy: a national survey. Lancet 1980; ii: 842-44. 3. Canny GJ, Corey M, Livingstone RA, et al. Pregnancy and cystic fibrosis. Obstet Gynecol 1991; 77: 850-53. 4. Kitzis A, Chomel JC, Kaplan JC, et al. Unusual segregation of cystic fibrosis allele to males. Nature 1988; 333: 215. 5. Kitzis A, Chomel JC, Haliassos A, et al. Unusual segregation of cystic fibrosis alleles. Nature 1988; 336: 316. 6. Pritchard DJ. Cystic fibrosis allele frequency, sex ratio anomalies and fertility: a new theory for the dissemination of mutant alleles. Hum Genet 1991; 87: 671-76.
Ciprofloxacin and typhoid fever we suggested that physicians in the UK using ciprofloxacin for the treatment of typhoid fever, especially for patients coming from areas where chloramphenicol-resistant strains have recently been reported.! This suggestion was based on our observation that, in 1990, 20% of Salmonella typhi isolated in the UK were chloramphenicol-resistant and over 80% of such strains were also resistant to ampicillin and trimethoprim. Reservations about the promotion of ciprofloxacin as a first-line drug for the treatment of typhoid in developing countries have been expressed,2 and we must emphasise that we did not recommend that ciprofloxacin should be routinely used for the
48 CHLORAM PH ENICOL-RESISTANTS TYPHI IN UK, 1991
C= chloramphenicol; A = ampicillin; Tm=tnmethoprim.
In 1991, equal proportions (42%) had a history of Pakistan or India. Chloramphenicol-resistant strains of phage types Mland Elhave also been isolated from patients with a history of return travel from other countries (table), and we have recently received multiresistant strains of these phage types from Australia, isolated from patients infected in Pakistan (Ml) or India
respectively. travel
to
(El). Chloramphenicol-resistant S typhi has not decreased in incidence in the UK in 1991 and we see no reason to change our recommendation about ciprofloxacin. It is, however, of concern that resistance to this important antimicrobial has now been found in an isolate of multiresistant S typhi. Division of Enteric Pathogens, Central Public Health Laboratory, London NW9 5HT, UK
B. ROWE L. R. WARD E. J. THRELFALL
B, Ward LR, Threlfall EJ. Treatment of multiresistant typhoid fever. Lancet 1991; 337: 1442. 2. Kumar PD. Ciprofloxacin for typhoid fever. Lancet 1991; 338: 1143. 3. Panigrahi D, Roy P, Sehgal R. Ciprofloxacin for typhoid fever. Lancet 1991; 338: 1601. 1. Rowe
SIR,-In June, 1991,
should consider
of typhoid.3 In 1991,48 of 226 (21 %) patients in the UK with S typhi were infected with chloramphenicol-resistant strains and, of these, 41 (85%) were resistant to ampicillin (A) and 42 (87%) to trimethoprim (Tm) (table). 25 (52%) strains belonged to Vi phage type Mland 20 (42%) to phage type El. Most patients from whom phage type Ml was isolated had recently returned from Pakistan and those with phage type Efrom India. However, 5 patients with phage type Ml did not have a history of recent foreign travel and had been infected in an outbreak associated with a take-away restaurant in north London in January, 1991. Although S typhi was not isolated from staff in the restaurant, some of the staff had lately returned from Pakistan. Strains from this outbreak were resistant to chloramphenicol, streptomycin, and tetracyclines (R-type CST) but sensitive to A and Tm. By contrast, most strains of phage types Ml and El from returning travellers were of R-type ACSSuTTm (Su sulphonamides). In all chloramphenicol-resistant strains of phage types Ml and El, the complete spectrum of resistance was encoded by incompatibility group (Inc) HI plasmids with molecular weights ranging from about 110 MDa (R-type CST) to 120 MDa (R-type ACSSuTTm). Besides being resistant to ACSSuTTm, 1 strain of phage-type El isolated from a one-year-old child infected in India was also resistant to nalidixic acid at 20 mg/1 and to ciprofloxacin at 0-30 mg/l; a nalidixic-acid-resistant control strain of Escherichia coli K12 was sensitive to ciprofloxacin at 0-10 mg/l. Resistance to nalidixic acid and ciprofloxacin in the strain of S typhi resistant to these antimicrobials was not plasmid-encoded. In 1990, 74% and 20% of patients with chloramphenicolresistant S typhi had a history of travel to Pakistan and India, treatment
=
SIR,-Dr Panigrahi and colleagues (Dec 21/28, p 1601) misinterpreted my comments regarding the use of ciprofloxacin in typhoid fever (Nov 2, p 1143). At our centre also, only 21 -8% strains of Salmonella typhi were sensitive to chloramphenicol but we felt that this might not reflect the situation in general practice, because the use of empirical therapy is prevalent in developing countries.
highlight the fact that multiresistance was not S typhi strains and we still encounter chloramphenicol-sensitive S typhi with good clinical response. Rowe et all may be right in recommending ciprofloxacin as the first-line drug in the UK, where only a handful of cases are encountered, mostly caused by multiresistant strains. We wanted to point out the hazard of translating this advice directly to thousands of patients in developing countries where chloramphenicol could be We also wanted to absolute among
given a fair trial. I agree with Panigrahi and colleagues’ observations on the increasing incidence of chloramphenicol (and multi) resistance. My point was that not every case of typhoid fever in developing countries needs to be treated with ciprofloxacin. Department of Medicine, Medical College, Calicut, Kerala, India
P. DILEEP KUMAR
1. Rowe B, Ward LR, Threlfall EH. Treatment of multiresistant typhoid fever. Lancet
1991; 337: 1422.
Genetic relation between Vibrio cholerae 01 strains in Ecuador and
Bangladesh
SiR,—The present South American cholera epidemic broke out in Peru in January, 1991, and is the first such outbreak in that continent during this century. The causative agent has been identified as Vibrio cholerae 01biotype El Tor, serotype Inaba.’ Cholera is endemic in Bangladesh, and shows two peaks-one in the hot season (March to June) and the other in the post-monsoon season (September to December). The seventh pandemic strain of El Tor V cholerae 01reached Bangladesh in the middle of 1973, and cholera has become permanently established there. In the aftermath of the devastating cyclone that hit the coastal areas of Bangladesh in April, 1991, there has been an outbreak of cholera
741
Experience with the subunit influenza vaccine shows a favourable safety profile. Out of 40 million vaccinations with the subunit vaccine (Influvac) since 1981, only 89 serious signs and symptoms from 65 subjects were reported to the manufacturer (Solvay Duphar, Netherlands).’ Of these adverse events, 8 were related to the respiratory system, including 5 cases of asthma exacerbations. Although we do not know how many of the 40 million vaccine doses were given to asthmatic patients, we may assume that this number is considerable because of specific inclusion of asthmatics in the high-risk patients for whom annual influenza vaccinations are
Chromosomal DNA extracted from strains of V cholerae 01, biotype E)Tor, serotype, )naba, isolated in 1991 from patients with diarrhoea in Ecuador (lanes 1---4) and Bangladesh (lanes
5-9). III-digested chromosomal DNA, hybridised with 32pdeoxycytidine triphosphate labelled 7 5-kb Bam Ht fragment from cloned rRNA gene probe, pKK 3535. Hind
due to El Tor biotype, both Inaba and Ogawa serotypes, in these areas. We have compared 5 strains of Inaba serotypes isolated in June and July, 1991, from this outbreak with 4 strains of Inaba serotype isolated from cases of cholera in Ecuador in April, 1991, to see if any clonal relation existed between the strains causing epidemics in the two distant continents. The strains were examined by Southern blots of Hind III digested chromosomal DNA probed for conserved rRNA genes with a cloned rRNA gene probe, derived from pKK 3535.3 The 4 Ecuadorian strains (figure, lanes 1-4) and the 5 Bangladeshi strains (lanes 5-9) produced identical Hind III cleavage patterns of their rRNA genes, suggesting genetic identity for V cholerae 01 strains causing epidemics in Bangladesh and Ecuador. In a recent report,4 strains of V cholerae 01 from Peru were genetically different from the V cholerae 01 strains that caused disease in the US gulf coast, but were related to strains from Malavi and Truk, which are thought to be part of the expanding seventh pandemic area. Our data lend further support to the notion that the South American cholera outbreak is attributable to the strain of V cholerae 01 that is causing the seventh pandemic and which is continuing to invade new territories. Dr Alfredo Davilo, National Institute of Health,
Guiyaquil, Ecuador,
supplied 4 strains of Inaba serotype. International Centre for Diarrhoeal Disease Research, Bangladesh ICDDR,B, Dhaka 1000, Bangladesh
SHAH M. FARUQUE
JOHN ALBERT
1. Centers for Disease Control. Update: cholera outbreak: Peru, Ecuador, and Colombia. MMWR 1991; 40: 225-27. 2. Glass RI, Becker S, Huq MI, et al. Endemic cholera in rural Bangladesh, 1966-1980.
Am J Epidemiol 1982; 116: 959-70. 3. Stull TL, Li Puma JJ, Edlind TD. A broad spectrum probe for molecular epidemiology of bacteria ribosomal RNA. J Infect Dis 1988; 157: 280-86. 4. Wachsmuth IK, Bopp CA, Fields PI, Carrilo C. Difference between toxigenic Vibrio cholerae O1 from South American and US gulf coast. Lancet 1991; 337: 1097-98.
Influenza vaccination in asthma SIR,-Dr Hassan and colleagues (Jan 18, p 194) report exacerbations of asthma in
some of their patients and therefore "do not annual influenza vaccine in stable asthmatics". Although case reports are important in generating hypotheses, they can never be used to prove them. A cause-effect relation between vaccination and aggravation of asthma has not been established, as pointed out in the reply by Dr Ong (Feb 8, p 367). Application of these findings to a whole population group can be hazardous for individual patients who might, therefore, not receive vaccination.
recommend
an
recommended. We agree with Hassan et al about the favourable side-effect profile of influenza subunit vaccine. In clinical studies of 2038 healthy volunteers, 695 (34%) reported local reactions (mainly pain at site of the injection) and 303 (15%) systemic reactions (mainly headache). In 1931 (95%) subjects, the reported reactions did not cause inconvenience. In a placebo-controlled study in elderly subjects, Margolis et aP found no significant differences between trivalent influenza split vaccine and placebo with respect to any local or systemic reaction apart from a sore arm (20%). Despite occasional serious adverse events, such as those reported by Hassan et al, our data demonstrate the safety and tolerance of the influenza subunit vaccine and do not justify Hassan and colleagues’ statement that "influenza vaccines have many side-effects". Despite the case reports by these workers, the established safety of influenza vaccines justifies present public health recommendations3.4 that at least 80% of high-risk patients, including asthmatics, should be immunised annually to reduce the risks of influenza-associated
complications. Adverse
Drug Experience Unit, Solvay Duphar, 1380 DA Weesp, Netherlands
A. M. PALACHE J. W. VD VELDEN
1. Palache AM. Influenza vaccination. The effect of dose and age on the antibody response: a methodological evaluation of serological vaccination studies. Erasmus University, Rotterdam, Netherlands, PhD thesis, 1991. 2. Margolis KL, Nichol KL, Poland GA, Pluhar RE. Frequency of adverse reactions to influenza vaccine in the elderly: a randomized, placebo-controlled trial. JAMA
1990; 254: 1139-41. 3. Advisory Committee on Influenza Prevention. MMWR 1987; 36: 373-87. 4. Calman KC. Influenza immunisation. London: Department of Health, PL/CMO(91) 13; Oct 8, 1991.
Epoprostenol infusions in thrombotic microangiopathy of pregnancy haemolytic-uraemic syndrome (HUS) and thrombocytopenic purpura (TTP) are thrombotic microangiopathies in which there is extensive platelet aggregation within the microcirculation. The success of plasma exchange suggests a potent platelet aggregatory factor, and anti-platelet agents might be expected to be of benefit. We report a patient who was much improved after infusion of epoprostenol (prostacyclin). A 35-year-old woman presented in her second pregnancy. Eclampsia in her first pregnancy precipitated delivery by caesarean section. The second pregnancy progressed without incident up to 25 weeks, when she noticed severe ankle swelling. Her blood pressure (BP) was 150/ 100 mm Hg and she had 2 + proteinuria. SiR,-Both
thrombotic
She was admitted for bed rest. Ultrasound scan revealed a small-for-dates fetus and normal-sized kidneys. Her BP did not settle so she was started on methyldopa and the anti-platelet agent sulphinpyrazone. Despite this, her BP remained above 110 mm Hg diastolic. Her haemoglobin (Hb) fell to 108 g/dl, platelets dropped to 87 x 109/l, fibrinogen degradation products (FDP) were 10-40 Jlgjml, and fragmented red blood cells were seen on the blood film. Thrombotic microangiopathy superimposed on pregnancyinduced hypertension was diagnosed, and on day 6 she was started on an infusion of epoprostenol 2 ng/kg per min, which was increased to 20 ng/kg over 24 h. The infusion appeared to control her BP and her Hb and platelet count rose (figure). The infusion was stopped and she went home for 2 days. On her return her diastolic BP had risen to 100 mm Hg and her platelet count had fallen; both measures improved when epoprostenol was restarted. An ultrasound scan in the 28th week demonstrated oligohydramnios and a fetal size compatible with 25-26 weeks. A girl was delivered by caesarean
healthy and heterozygous for CF. The finding that unaffected heterozygous children of women with CF are mainly male was unexpected. The mechanism for this male dominance remains were
obscure. The two North American studies did not state the sex of the infants,2,3 and other reports provide such data only for families of children with CF, and not for children of CF mothers. Tests on healthy siblings of CF patients showed an unexpected sex ratio, with an excess of heterozygous boys inheriting the CF gene either from their father or their mother.4,5 Investigations of siblings with partners heterozygous for CF make a sex-related selection after fertilisation probable.6 However, a sex-related selective influence before fertilisation may occur as a result of the highly viscous, low-water-content cervical mucus of women with CF, which may form a barrier to sperm. A hitherto unknown heterozygous advantage might be present in Y chromosome carriers. Clinic for Child and Youth Medicine, Im Borntal 1-7, W-3423 Bad Sachsa, Germany
O. METZ
1. Metz OW, Metz S. Schwangerschaft und Geburt bei Mukoviszidose: Resultate der Deutschland-Studie. Klin Paed (in press). 2. Cohen LF, DiSant’Agnese PA, Friedlander J. Cystic fibrosis and pregnancy: a national survey. Lancet 1980; ii: 842-44. 3. Canny GJ, Corey M, Livingstone RA, et al. Pregnancy and cystic fibrosis. Obstet Gynecol 1991; 77: 850-53. 4. Kitzis A, Chomel JC, Kaplan JC, et al. Unusual segregation of cystic fibrosis allele to males. Nature 1988; 333: 215. 5. Kitzis A, Chomel JC, Haliassos A, et al. Unusual segregation of cystic fibrosis alleles. Nature 1988; 336: 316. 6. Pritchard DJ. Cystic fibrosis allele frequency, sex ratio anomalies and fertility: a new theory for the dissemination of mutant alleles. Hum Genet 1991; 87: 671-76.
Ciprofloxacin and typhoid fever we suggested that physicians in the UK using ciprofloxacin for the treatment of typhoid fever, especially for patients coming from areas where chloramphenicol-resistant strains have recently been reported.! This suggestion was based on our observation that, in 1990, 20% of Salmonella typhi isolated in the UK were chloramphenicol-resistant and over 80% of such strains were also resistant to ampicillin and trimethoprim. Reservations about the promotion of ciprofloxacin as a first-line drug for the treatment of typhoid in developing countries have been expressed,2 and we must emphasise that we did not recommend that ciprofloxacin should be routinely used for the
48 CHLORAM PH ENICOL-RESISTANTS TYPHI IN UK, 1991
C= chloramphenicol; A = ampicillin; Tm=tnmethoprim.
In 1991, equal proportions (42%) had a history of Pakistan or India. Chloramphenicol-resistant strains of phage types Mland Elhave also been isolated from patients with a history of return travel from other countries (table), and we have recently received multiresistant strains of these phage types from Australia, isolated from patients infected in Pakistan (Ml) or India
respectively. travel
to
(El). Chloramphenicol-resistant S typhi has not decreased in incidence in the UK in 1991 and we see no reason to change our recommendation about ciprofloxacin. It is, however, of concern that resistance to this important antimicrobial has now been found in an isolate of multiresistant S typhi. Division of Enteric Pathogens, Central Public Health Laboratory, London NW9 5HT, UK
B. ROWE L. R. WARD E. J. THRELFALL
B, Ward LR, Threlfall EJ. Treatment of multiresistant typhoid fever. Lancet 1991; 337: 1442. 2. Kumar PD. Ciprofloxacin for typhoid fever. Lancet 1991; 338: 1143. 3. Panigrahi D, Roy P, Sehgal R. Ciprofloxacin for typhoid fever. Lancet 1991; 338: 1601. 1. Rowe
SIR,-In June, 1991,
should consider
of typhoid.3 In 1991,48 of 226 (21 %) patients in the UK with S typhi were infected with chloramphenicol-resistant strains and, of these, 41 (85%) were resistant to ampicillin (A) and 42 (87%) to trimethoprim (Tm) (table). 25 (52%) strains belonged to Vi phage type Mland 20 (42%) to phage type El. Most patients from whom phage type Ml was isolated had recently returned from Pakistan and those with phage type Efrom India. However, 5 patients with phage type Ml did not have a history of recent foreign travel and had been infected in an outbreak associated with a take-away restaurant in north London in January, 1991. Although S typhi was not isolated from staff in the restaurant, some of the staff had lately returned from Pakistan. Strains from this outbreak were resistant to chloramphenicol, streptomycin, and tetracyclines (R-type CST) but sensitive to A and Tm. By contrast, most strains of phage types Ml and El from returning travellers were of R-type ACSSuTTm (Su sulphonamides). In all chloramphenicol-resistant strains of phage types Ml and El, the complete spectrum of resistance was encoded by incompatibility group (Inc) HI plasmids with molecular weights ranging from about 110 MDa (R-type CST) to 120 MDa (R-type ACSSuTTm). Besides being resistant to ACSSuTTm, 1 strain of phage-type El isolated from a one-year-old child infected in India was also resistant to nalidixic acid at 20 mg/1 and to ciprofloxacin at 0-30 mg/l; a nalidixic-acid-resistant control strain of Escherichia coli K12 was sensitive to ciprofloxacin at 0-10 mg/l. Resistance to nalidixic acid and ciprofloxacin in the strain of S typhi resistant to these antimicrobials was not plasmid-encoded. In 1990, 74% and 20% of patients with chloramphenicolresistant S typhi had a history of travel to Pakistan and India, treatment
=
SIR,-Dr Panigrahi and colleagues (Dec 21/28, p 1601) misinterpreted my comments regarding the use of ciprofloxacin in typhoid fever (Nov 2, p 1143). At our centre also, only 21 -8% strains of Salmonella typhi were sensitive to chloramphenicol but we felt that this might not reflect the situation in general practice, because the use of empirical therapy is prevalent in developing countries.
highlight the fact that multiresistance was not S typhi strains and we still encounter chloramphenicol-sensitive S typhi with good clinical response. Rowe et all may be right in recommending ciprofloxacin as the first-line drug in the UK, where only a handful of cases are encountered, mostly caused by multiresistant strains. We wanted to point out the hazard of translating this advice directly to thousands of patients in developing countries where chloramphenicol could be We also wanted to absolute among
given a fair trial. I agree with Panigrahi and colleagues’ observations on the increasing incidence of chloramphenicol (and multi) resistance. My point was that not every case of typhoid fever in developing countries needs to be treated with ciprofloxacin. Department of Medicine, Medical College, Calicut, Kerala, India
P. DILEEP KUMAR
1. Rowe B, Ward LR, Threlfall EH. Treatment of multiresistant typhoid fever. Lancet
1991; 337: 1422.
Genetic relation between Vibrio cholerae 01 strains in Ecuador and
Bangladesh
SiR,—The present South American cholera epidemic broke out in Peru in January, 1991, and is the first such outbreak in that continent during this century. The causative agent has been identified as Vibrio cholerae 01biotype El Tor, serotype Inaba.’ Cholera is endemic in Bangladesh, and shows two peaks-one in the hot season (March to June) and the other in the post-monsoon season (September to December). The seventh pandemic strain of El Tor V cholerae 01reached Bangladesh in the middle of 1973, and cholera has become permanently established there. In the aftermath of the devastating cyclone that hit the coastal areas of Bangladesh in April, 1991, there has been an outbreak of cholera
741
Experience with the subunit influenza vaccine shows a favourable safety profile. Out of 40 million vaccinations with the subunit vaccine (Influvac) since 1981, only 89 serious signs and symptoms from 65 subjects were reported to the manufacturer (Solvay Duphar, Netherlands).’ Of these adverse events, 8 were related to the respiratory system, including 5 cases of asthma exacerbations. Although we do not know how many of the 40 million vaccine doses were given to asthmatic patients, we may assume that this number is considerable because of specific inclusion of asthmatics in the high-risk patients for whom annual influenza vaccinations are
Chromosomal DNA extracted from strains of V cholerae 01, biotype E)Tor, serotype, )naba, isolated in 1991 from patients with diarrhoea in Ecuador (lanes 1---4) and Bangladesh (lanes
5-9). III-digested chromosomal DNA, hybridised with 32pdeoxycytidine triphosphate labelled 7 5-kb Bam Ht fragment from cloned rRNA gene probe, pKK 3535. Hind
due to El Tor biotype, both Inaba and Ogawa serotypes, in these areas. We have compared 5 strains of Inaba serotypes isolated in June and July, 1991, from this outbreak with 4 strains of Inaba serotype isolated from cases of cholera in Ecuador in April, 1991, to see if any clonal relation existed between the strains causing epidemics in the two distant continents. The strains were examined by Southern blots of Hind III digested chromosomal DNA probed for conserved rRNA genes with a cloned rRNA gene probe, derived from pKK 3535.3 The 4 Ecuadorian strains (figure, lanes 1-4) and the 5 Bangladeshi strains (lanes 5-9) produced identical Hind III cleavage patterns of their rRNA genes, suggesting genetic identity for V cholerae 01 strains causing epidemics in Bangladesh and Ecuador. In a recent report,4 strains of V cholerae 01 from Peru were genetically different from the V cholerae 01 strains that caused disease in the US gulf coast, but were related to strains from Malavi and Truk, which are thought to be part of the expanding seventh pandemic area. Our data lend further support to the notion that the South American cholera outbreak is attributable to the strain of V cholerae 01 that is causing the seventh pandemic and which is continuing to invade new territories. Dr Alfredo Davilo, National Institute of Health,
Guiyaquil, Ecuador,
supplied 4 strains of Inaba serotype. International Centre for Diarrhoeal Disease Research, Bangladesh ICDDR,B, Dhaka 1000, Bangladesh
SHAH M. FARUQUE
JOHN ALBERT
1. Centers for Disease Control. Update: cholera outbreak: Peru, Ecuador, and Colombia. MMWR 1991; 40: 225-27. 2. Glass RI, Becker S, Huq MI, et al. Endemic cholera in rural Bangladesh, 1966-1980.
Am J Epidemiol 1982; 116: 959-70. 3. Stull TL, Li Puma JJ, Edlind TD. A broad spectrum probe for molecular epidemiology of bacteria ribosomal RNA. J Infect Dis 1988; 157: 280-86. 4. Wachsmuth IK, Bopp CA, Fields PI, Carrilo C. Difference between toxigenic Vibrio cholerae O1 from South American and US gulf coast. Lancet 1991; 337: 1097-98.
Influenza vaccination in asthma SIR,-Dr Hassan and colleagues (Jan 18, p 194) report exacerbations of asthma in
some of their patients and therefore "do not annual influenza vaccine in stable asthmatics". Although case reports are important in generating hypotheses, they can never be used to prove them. A cause-effect relation between vaccination and aggravation of asthma has not been established, as pointed out in the reply by Dr Ong (Feb 8, p 367). Application of these findings to a whole population group can be hazardous for individual patients who might, therefore, not receive vaccination.
recommend
an
recommended. We agree with Hassan et al about the favourable side-effect profile of influenza subunit vaccine. In clinical studies of 2038 healthy volunteers, 695 (34%) reported local reactions (mainly pain at site of the injection) and 303 (15%) systemic reactions (mainly headache). In 1931 (95%) subjects, the reported reactions did not cause inconvenience. In a placebo-controlled study in elderly subjects, Margolis et aP found no significant differences between trivalent influenza split vaccine and placebo with respect to any local or systemic reaction apart from a sore arm (20%). Despite occasional serious adverse events, such as those reported by Hassan et al, our data demonstrate the safety and tolerance of the influenza subunit vaccine and do not justify Hassan and colleagues’ statement that "influenza vaccines have many side-effects". Despite the case reports by these workers, the established safety of influenza vaccines justifies present public health recommendations3.4 that at least 80% of high-risk patients, including asthmatics, should be immunised annually to reduce the risks of influenza-associated
complications. Adverse
Drug Experience Unit, Solvay Duphar, 1380 DA Weesp, Netherlands
A. M. PALACHE J. W. VD VELDEN
1. Palache AM. Influenza vaccination. The effect of dose and age on the antibody response: a methodological evaluation of serological vaccination studies. Erasmus University, Rotterdam, Netherlands, PhD thesis, 1991. 2. Margolis KL, Nichol KL, Poland GA, Pluhar RE. Frequency of adverse reactions to influenza vaccine in the elderly: a randomized, placebo-controlled trial. JAMA
1990; 254: 1139-41. 3. Advisory Committee on Influenza Prevention. MMWR 1987; 36: 373-87. 4. Calman KC. Influenza immunisation. London: Department of Health, PL/CMO(91) 13; Oct 8, 1991.
Epoprostenol infusions in thrombotic microangiopathy of pregnancy haemolytic-uraemic syndrome (HUS) and thrombocytopenic purpura (TTP) are thrombotic microangiopathies in which there is extensive platelet aggregation within the microcirculation. The success of plasma exchange suggests a potent platelet aggregatory factor, and anti-platelet agents might be expected to be of benefit. We report a patient who was much improved after infusion of epoprostenol (prostacyclin). A 35-year-old woman presented in her second pregnancy. Eclampsia in her first pregnancy precipitated delivery by caesarean section. The second pregnancy progressed without incident up to 25 weeks, when she noticed severe ankle swelling. Her blood pressure (BP) was 150/ 100 mm Hg and she had 2 + proteinuria. SiR,-Both
thrombotic
She was admitted for bed rest. Ultrasound scan revealed a small-for-dates fetus and normal-sized kidneys. Her BP did not settle so she was started on methyldopa and the anti-platelet agent sulphinpyrazone. Despite this, her BP remained above 110 mm Hg diastolic. Her haemoglobin (Hb) fell to 108 g/dl, platelets dropped to 87 x 109/l, fibrinogen degradation products (FDP) were 10-40 Jlgjml, and fragmented red blood cells were seen on the blood film. Thrombotic microangiopathy superimposed on pregnancyinduced hypertension was diagnosed, and on day 6 she was started on an infusion of epoprostenol 2 ng/kg per min, which was increased to 20 ng/kg over 24 h. The infusion appeared to control her BP and her Hb and platelet count rose (figure). The infusion was stopped and she went home for 2 days. On her return her diastolic BP had risen to 100 mm Hg and her platelet count had fallen; both measures improved when epoprostenol was restarted. An ultrasound scan in the 28th week demonstrated oligohydramnios and a fetal size compatible with 25-26 weeks. A girl was delivered by caesarean
